MALDI Mass Spectrometry Imaging of N-Linked Glycans in Cancer Tissues

Adv Cancer Res. 2017:134:85-116. doi: 10.1016/bs.acr.2016.11.009. Epub 2016 Dec 20.

Abstract

Glycosylated proteins account for a majority of the posttranslation modifications of cell surface, secreted, and circulating proteins. Within the tumor microenvironment, the presence of immune cells, extracellular matrix proteins, cell surface receptors, and interactions between stroma and tumor cells are all processes mediated by glycan binding and recognition reactions. Changes in glycosylation during tumorigenesis are well documented to occur and affect all of these associated adhesion and regulatory functions. A MALDI imaging mass spectrometry (MALDI-IMS) workflow for profiling N-linked glycan distributions in fresh/frozen tissues and formalin-fixed paraffin-embedded tissues has recently been developed. The key to the approach is the application of a molecular coating of peptide-N-glycosidase to tissues, an enzyme that cleaves asparagine-linked glycans from their protein carrier. The released N-linked glycans can then be analyzed by MALDI-IMS directly on tissue. Generally 40 or more individual glycan structures are routinely detected, and when combined with histopathology localizations, tumor-specific glycans are readily grouped relative to nontumor regions and other structural features. This technique is a recent development and new approach in glycobiology and mass spectrometry imaging research methodology; thus, potential uses such as tumor-specific glycan biomarker panels and other applications are discussed.

Keywords: Biomarkers; Formalin-fixed paraffin-embedded tissue; Fucosylation; Glycobiology; Glycomics; Glycoproteins; MALDI imaging mass spectrometry; N-linked glycosylation; Tumor antigens glycoprotein.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Glycosylation
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Molecular Imaging / methods*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Polysaccharides / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*

Substances

  • Biomarkers, Tumor
  • Polysaccharides